Oncology Drug Reference Sheet: Erdafitinib
Erdafitinib (Balversa™) is the first targeted therapy that the U.S. Food and Drug Administration (FDA) approved for treatment of metastatic bladder cancer.
It received accelerated approval (https://www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-therapy-metastatic-bladder-cancer) in April 2019 based on tumor response rate results from a phase II, multicenter, open-label, single-arm study in 87 patients with disease that had progressed on or after at least one prior chemotherapy and that had at least one of the following genetic alterations: FGFR3 gene mutations (R248C, S249C, G370C, Y373C) or FGFR gene fusions (FGFR3-TACC3, FGFR3-BAIAP2L1, FGFR2-BICC1, FGFR2-CASP7), as determined by a clinical trial assay. The results demonstrated a 32.2% objective response rate as assessed by a blinded independent review committee. Responders included patients who had previously not responded (https://www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-therapy-metastatic-bladder-cancer) to anti-PD-L1/PD-1 therapy.
Targeted therapy/fibroblast growth factor receptor (FGFR) kinase inhibitor
Erdafitinib is indicated for treatment of adult patients with locally advanced or metastatic urothelial carcinoma that has susceptible FGFR3 or FGFR2 genetic alterations and progressed during or following at least one line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy (http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/BALVERSA-pi.pdf).
Select patients for therapy based on an FDA-approved companion diagnostic for erdafitinib, which looks for evidence of a susceptible FGFR3 or FGFR2 mutation or gene fusion within the tumor specimen.
Dosing and Administration
Erdafitinib’s recommended starting dose is 8 mg (two 4 mg tablets) orally once daily, with a dose increase to 9 mg (three 3 mg tablets) once daily based on serum phosphate levels and tolerability at 14–21 days. Swallow tablets once daily whole with or without food. If vomiting occurs any time after taking erdafitinib, do not take an additional dose; continue with the planned dose the next day. Treatment should continue until disease progression or unacceptable toxicity occurs (http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/BALVERSA-pi.pdf).
The most common adverse reactions (http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/BALVERSA-pi.pdf) (≥ 20%) were increased phosphate, stomatitis, fatigue, increased creatinine, diarrhea, dry mouth, onycholysis, increased alanine aminotransferase, increased alkaline phosphatase, decreased sodium, decreased appetite, decreased albumin, dysgeusia, decreased hemoglobin, dry skin, increased aspartate aminotransferase, decreased magnesium, dry eyes, alopecia, palmar-plantar erythrodysesthesia syndrome, constipation, decreased phosphate, abdominal pain, increased calcium, nausea, and musculoskeletal pain.
- Erdafitinib can cause central serous retinopathy/retinal pigment epithelial detachment. Perform monthly ophthalmologic examinations during the first four months of treatment, every three months after, and any time that visual symptoms occur.
- Increases in phosphate levels are a pharmacodynamic effect of erdafitinib. Assess serum phosphate levels 14–21 days after initiating treatment. Increase the dose of erdafitinib to 9 mg once daily if serum phosphate level is less than 5.5 mg/dl, patients have no ocular disorders, and any adverse reactions are less than grade 2. Monitor phosphate levels monthly for hyperphosphatemia.
- Review medication lists for drug interactions that affect erdafitinib (see page 4 of the package insert (http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/BALVERSA-pi.pdf)) like strong CYP2C9 or CYP3A4 inhibitors, strong CYP2C9 or CYP3A4 inducers, moderate CYP2C9 or CYP3A4 inducers, or serum phosphate level-altering agents as well as drugs that erdafitinib can affect like CYP3A4 substrates, OCT2 substrates, or P-glycoprotein (P-gp) substrates.
Erdafitinib can cause fetal harm. Complete a pregnancy test prior to starting therapy. Advise patients of the potential risk to the fetus and to use effective contraception
- Evidence of a susceptible FGFR3 or FGFR2 mutation or gene fusion within the tumor specimen is necessary to identify patients for whom erdafitinib treatment is indicated.
- Contact your healthcare provider if you experience any visual changes or progressive or intolerable skin, mucous, or nail disorders.
- To prevent or treat dry eyes, use artificial tear substitutes, hydrating or lubricating eye gels, or ointments at least every two hours while awake.
- Your healthcare provider will assess serum phosphate levels 14–21 days after initiating treatment, then monthly, and will adjust the dose if needed.
- Inform your healthcare providers of all concomitant medications, including prescription medicines, over-the-counter drugs, and herbal products.
- Erdafitinib is associated with potential risk to a fetus. Inform your healthcare providers of a known or suspected pregnancy.
- Men and women of reproductive potential must use effective contraception during treatment and for one month after the last dose of erdafitinib.
- Do not breastfeed during treatment with erdafitinib and for one month after the last dose.
No clinically meaningful trends in the pharmacokinetics of erdafitinib were observed based on age (21–88 years), sex, race, or body weight (36–132 kg).
Erdafitinib is considered a hazardous drug because of its reproductive risk of embryo-fetal toxicity. Women of childbearing potential should inform providers of a known or suspected pregancy and have a pregnancy test before beginning treatment. Men and women must use effective contraception during treatment and for one month following the last dose. Women receiving erdafitinib should not breastfeed their children during treatment and for one month after their last dose.
Patient Assistance Programs
For patient support for erdafitinib, call 877-757-0667 or visit JanssenPrescriptionAssistance.com (http://www.janssenprescriptionassistance.com/).